Treatment options for the management of acute leukaemia relapsing following an allogeneic transplant

Shaw, Bronwen E.; Russell, Nigel H.

doi:10.1038/sj.bmt.1705888

Cited by 31 publications

(24 citation statements)

References 92 publications

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“…Treatment options for these patients have been reviewed by Shaw and Russell. 23 They concluded that the main strategies aim at achieving CR by disease-directed therapy and at exploiting the graft-versus-leukemia-effect by immunomodulatory interventions, such as donor lymphocyte infusion (DLI). However, these conclusions were based on small patient numbers in various studies or on retrospective data analyses from registries.…”

Section: Discussionmentioning

confidence: 99%

Consequent and intensified relapse therapy improved survival in pediatric AML: results of relapse treatment in 379 patients of three consecutive AML-BFM trials

et al. 2010

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Relapse remains the major cause of treatment failure in pediatric acute myeloid leukemia (AML). We analyzed the clinical characteristics, treatment response to relapse treatment and overall survival (OS) of 379 children with AML relapse treated according to three consecutive frontline protocols of the AML-Berlin/Frankfurt/Muenster study group (AML-BFM-87/-93/-98). Of 313 treated patients with data on remission status, 198 children (63%) achieved a second complete remission (CR2). There were no significant differences in remission rates and OS for the intensive reinduction treatment schedules used.The 5-year OS rate was 23% for the total group and 29% for patients treated with curative intent. OS rates increased with study periods from 18 to 34% (P log rank ¼ 0.012), whereas the proportion of patients receiving only palliative treatment decreased from 23 to 11% (P CMH ¼ 0.005). Late relapse, no allogeneic stem cell transplantation (SCT) in CR1, age o10 years and favorable cytogenetics were independent favorable prognostic factors for survival. Achievement of CR2 was the most important prognostic factor (OS 44 vs 3%; P log rank o0.0001). Overall, one-third of children with relapsed AML can be cured today. SCT in CR2 is recommended for most patients, although its impact on CR2 is discussed.

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Section: Discussionmentioning

confidence: 99%

Consequent and intensified relapse therapy improved survival in pediatric AML: results of relapse treatment in 379 patients of three consecutive AML-BFM trials

et al. 2010

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“…Preclinical studies on combinations of IFN-a and other antileukemic agents offer new opportunities for improving its clinical applicability. 56,80 Such combinatorial approaches have also been reported to be successful in AML patients relapsing after HSCT, 93 arguing for the exploration of new combination regimens. Future research should also focus on identifying the maximally effective IFN treatment scheme with respect to optimal dose, timing and treatment duration.…”

Section: 15mentioning

confidence: 99%

Interferon-α in acute myeloid leukemia: an old drug revisited

et al. 2011

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Interferon-a (IFN-a), a type I IFN, is a well-known antitumoral agent. The investigation of its clinical properties in acute myeloid leukemia (AML) has been prompted by its pleiotropic antiproliferative and immune effects. So far, integration of IFN-a in the therapeutic arsenal against AML has been modest in view of the divergent results of clinical trials. Recent insights into the key pharmacokinetic determinants of the clinical efficacy of IFN along with advances in its pharmaceutical formulation, have sparked renewed interest in its use. This paper reviews the possible applicability of IFN-a in the treatment of AML and provides a rational basis to re-explore its efficacy in clinical trials.

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“…10,13 The potential GVL or GVT effects of DLI make it one of the favored treatment choices for recurrent diseases. 14,15 Since Kolb et al first reported sustained remission after DLI in patients with CML relapse after allogeneic BMT in 1990, 16 unmanipulated DLI has become the mainstay allogeneic cellular therapy. However, owing to high risk of GVHD, 17,18 broad use of this monotherapy had been limited until 1996 when an Israeli group described a new approach using lymphocytes treated in vivo or in vitro with recombinant IL-2, by which better therapeutic response was achieved even in those who were previously resistant to unmanipulated DLI.…”

Section: Modified Therapeutic DLImentioning

confidence: 99%

“…These results suggest that low-dose MTX administration post mDLI could lead to stronger GVL effect and less DLI-associated GVHD. 51 Given the risk of high-intensity conditioning regimen and high TRM of a second transplant often chosen for a certain group of patients with relapsed diseases, 15,40,52,53 modified DLI described above could be worthy alternative approaches for those patients. 47 These approaches most likely exert their effect via modulating immune responses.…”

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confidence: 99%

New strategies of DLI in the management of relapse of hematological malignancies after allogeneic hematopoietic SCT

Chang

Zang

Xia

2015

Bone Marrow Transplant

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DLI is an effective strategy for patients with recurrent hematological malignancies after allogeneic hematopoietic SCT (allo-HSCT). DLI has been widely applied to boost the graft vs tumor (GVT) or GVL effects. However, given the potentially severe complications associated with conventional DLI and transient GVL effect, new strategies for DLI are emerging. In this review, we have discussed the recent important studies on DLI as a prophylactic or therapeutic modality for relapsed hematological disorders after allo-HSCT. The strategies to separate GVL from GVHD have also been discussed. Leukemia-targeting therapy and lymphodepletion combined with DLI, and prophylactic DLI after allo-HSCT are often employed for patients with high risk of relapse, which has been reviewed as well. In addition, we have also discussed the issues on DLI to be further addressed, such as the doses, timing and frequency of DLI in different clinical settings, leukemic antigen-specific DLI as well as how to augment GVL effect while attenuating GVHD.

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Treatment options for the management of acute leukaemia relapsing following an allogeneic transplant

Abstract: The management of acute leukaemia which relapses following an allogeneic stem cell transplant remains a major challenge. In this review we summarize the outcomes of the currently available treatment modalities and discuss emerging novel approaches.

Cited by 31 publications

References 92 publications

Consequent and intensified relapse therapy improved survival in pediatric AML: results of relapse treatment in 379 patients of three consecutive AML-BFM trials

Consequent and intensified relapse therapy improved survival in pediatric AML: results of relapse treatment in 379 patients of three consecutive AML-BFM trials

Interferon-α in acute myeloid leukemia: an old drug revisited

New strategies of DLI in the management of relapse of hematological malignancies after allogeneic hematopoietic SCT

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